Prevention of systemic clinical disease in MPS VII mice following AAV-mediated neonatal gene transfer

For many inborn errors of metabolism, early treatment is critical to preven t long-term developmental sequelae. We have previously shown that systemic treatment of neonatal mucopolysaccharidosis type VII (MPS VII) mice with re combinant adeno-associated virus (AAV) vectors results in relatively long-t erm expression of beta -glucuronidase (GUSB) in multiple tissues, and a red uction in lysosomal storage. Here, we demonstrate that therapeutic levels o f enzyme persist for at least 1 year following a single intravenous injecti on of virus in neonatal MPS VII mice. The level and distribution of GUSB ex pression achieved is sufficient to prevent the development of many aspects of clinical disease over the life of the animal. Following treatment, bone lengths, weights and retinal function were maintained at nearly normal leve ls throughout the life of the animal. In addition, significant improvements in survival and auditory function were seen in AAV-treated MPS VII mice wh en compared with untreated mutant siblings. These data suggest that AAV-med iated gene transfer in the neonatal period can lead to prevention of many o f the clinical symptoms associated with MPS VII in the murine model of this disease.